Elimination and replenishment of tricarboxylic acid-cycle intermediates in myocardium.
1. The contribution of Co2 fixation to the anaplerotic mechanisms in the myocardium was investigated in isolated perfused rat hearts. 2. K+-induced arrest of the heart was used to elicit a transition in the concentrations of the intermediates of the tricarboxylic acid cycle. 3. Incorporation of 14C from [14]bicarbonate into tricarboxylic acid-cycle intermediates was measured and the rates of the reactions of the cycle were estimated by means of a linear optimization program which solves the differential equations describing a simulation model of the tricarboxylic acid cycle and related reactions. 4. The results showed that the rate of CO2 fixation is dependent on the metabolic state of the myocardium. Upon a sudden diminution of cellular ATP consumption, the pool size of the tricarboxylic acid-cycle metabolites increased and the rate of label incorporation from [14C]bicarbonate into the cycle metabolites increased simultaneously. The computer model was necessary to separate the rapid equilibration between bicarbonate and some metabolites from the potentially anaplerotic reactions. The main route of anaplerosis during metabolite accumulation was through malate + oxaloacetate. Under steady-state conditions there was a constant net outward flow from the tricarboxylic acid cycle via the malate + oxaloacetate pool, with a concomitant anaplerotic flow from metabolites forming succinyl-CoA (3-carboxypropionyl-CoA).
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002952:Citric Acid Cycle; D003201:Computers; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D010071:Oxaloacetates / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D014233:Tricarboxylic Acids / Q000378:metabolism*
D001639:Bicarbonates; D008293:Malates; D010071:Oxaloacetates; D014233:Tricarboxylic Acids; D002245:Carbon Dioxide